tbuckley/cabot-search huggingface dataset:
Prediction of risk factors associated with readmission after robotic esophagectomy.
Authors: Kenneth Lee Meredith, Gabrielle LeBlanc, Caitlin Takahashi, Jamie Huston, Ravi Shridhar
Journal: Journal of Clinical Oncology (2023)

328 Background: Approximately, 20,640 new esophageal cancers (EC) will be diagnosed in 2022 and this will result in 16,410 deaths. Surgical resection remains the only potentially curative option, however significant morbidity and mortality ensues. Robotic approaches to esophageal resection have decreased overall length of hospitalizations. However, readmissions rates continue to be a significant concern. We sought to evaluate factors predicting readmission after robotic assisted trans-thoracic esophagectomy (RATE). Methods: Utilizing a prospectively maintained esophageal database, we identified patients with EC who underwent RATE between 2009-2022. We then stratified by readmissions, length of hospitalization and post-operative complications. Pre-operative, peri-operative and post-operative risk factors were identified as predictors of readmissions. Baseline univariate comparisons were made for continuous variables using both the Mann-Whitney U and Kruskal Wallis tests. Pearson’s Chi-square test was used to compare categorical variables. Multivariate analysis was performed identifying predictors of readmission. Results: We identified 312 patients, who underwent RATE with a median age of 68 (38-91). There were 29 (9.3%) patients who underwent readmission. There were no differences in age (p=0.10), gender (p=0.39) BMI (p=0.22), or histology (p=0.35) between patients that were readmitted and those that were not. ASA scores were higher in those that were readmitted p=0.01 compared to those who were not. The median length of hospitalization (LOH) was 8 (7-11) and did not differ between those that were re-admitted and those that were not p=0.79. The most common reasons for re-admissions were pulmonary 16 (5.1%), anastomotic leak 6 (1.9%), soft tissue infection 2 (0.6%), nutrition 3 (1%) and gastrointestinal 2 (0.6%). Pre-operative risk factors predictive of readmissions included cardiac disease p=0.002 and diabetes p=0.04. Operative risk factors: estimated blood loss p=0.9 and operative time p=0.24 did not predict readmission. Post-operative complications occurred in 93 (29.8%) of patients. Any post-operative complication p=0.32 did not predict re-admission with the exception of anastomotic leak p=0.04. Additionally, length of ICU did not differ between those re-admitted and those who were not, p=0.96. Ninety-day mortality was significantly higher in those that were re-admitted, 13.8% vs 4% in those that were not re-admitted, p=0.001. Multivariate analysis revealed that cardiac disease, diabetes, ASA score, and anastomotic leak were all predictors of readmission. Conclusions: Readmission after RATE remains low despite decreased LOH. Patients that are readmitted will have a significantly higher risk of mortality at 90-days. Pre-operative, peri-operative and post-operative factors can be used to accurately predict risk for readmission after robotic esophagectomy.
Phase II/III study of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA).
Authors: Van K. Morris, Greg Yothers, Scott Kopetz, Samuel A. Jacobs, Peter C. Lucas, Atif Iqbal, Patrick M Boland, Dustin A. Deming, Aaron James Scott, Howard John Lim, Theodore S. Hong, Norman Wolmark, Thomas J. George
Journal: Journal of Clinical Oncology (2023)

TPS259 Background: Detection of circulating tumor DNA (ctDNA) shed into the bloodstream represents a highly specific and sensitive approach for identifying microscopic or residual tumor cells after surgical resection. For patients (pts) with colon cancer (CC), the detection of ctDNA is associated with persistent disease after resection and outperforms traditional clinical and pathological features in prognosticating risk for recurrence. However, for pts with stage II CC, there are currently no validated biomarkers predicting benefit in identifying pts whose residual disease cancer be cleared by adjuvant chemotherapy. We hypothesize that for pts whose stage II colon cancer has been resected and who have no traditional high-risk features, a positive ctDNA status may identify those who will benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts (N=1,408) with resected stage II CC without traditional high-risk features and whom the evaluating oncologist deems suitable for active surveillance (i.e., not needing adjuvant chemotherapy) will be randomized 1:1 into 2 arms: standard-of-care/observation (Arm A), or prospective testing for ctDNA (Arm B). Postoperative blood will be analyzed for ctDNA with the Guardant Reveal assay, covering CC-relevant mutations and CC-specific methylation profiling. Pts in Arm B with ctDNA detected will be treated with 6 months of adjuvant (FOLFOX) chemotherapy. For all pts in Arm A, ctDNA status will be analyzed retrospectively at the time of endpoint analysis. The primary endpoints are clearance of ctDNA with adjuvant chemotherapy (phase II) and recurrence-free survival (RFS) for “ctDNA-detected” pts treated with or without adjuvant chemotherapy (phase III). Secondary endpoints will include time-to-event outcomes (OS, RFS, TTR) by ctDNA marker status and treatment, prevalence of detectable ctDNA in stage II CC, and rates of compliance with assigned intervention. Archived normal and matched tumor and blood samples will be collected for exploratory correlative research. Enrollment continues across North America to the 540-patient phase II endpoint. Support: U10CA180868, -180822; UG1CA189867; GuardantHealth. Clinical trial information: NCT04068103 .
Lower risk of depression after smoking cessation and alcohol abstinence in patients with gastric cancer who underwent gastrectomy: A population-based nationwide cohort study.
Authors: Bokyung Kim, Kyungdo Han, Hyunsoo Chung, Sang Gyun Kim, Soo-Jeong Cho
Journal: Journal of Clinical Oncology (2023)

314 Background: Although depression is associated with poor treatment outcomes and lower quality of life in cancer patients, little is known about whether lifestyle modifications could help prevent depression in these patients. This study aimed to identify the effect of lifestyle modifications such as smoking cessation, alcohol abstinence, and starting exercise on depression development in gastric cancer patients who underwent gastrectomy. Methods: Using the Korean National Health Insurance Service database, we identified gastric cancer patients who underwent gastrectomy between 2010 and 2017. Self-reported lifestyle behaviors within two years before and after gastrectomy were analyzed using health examination database. We classified the patients according to changes in lifestyle behaviors and compared their risk of developing depression. Results: Among 18,902 patients who underwent gastrectomy, 2,302 (12.19%) developed depression (26.00 per 1000 person-years). Smoking cessation (Hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.66-0.91) and alcohol abstinence (HR = 0.79, 95% CI: 0.69-0.90) were associated with reduced risk of depression development compared to persistent smoking and persistent drinking, respectively. Starting exercise was not associated with risk of depression. When lifestyle behaviors after gastrectomy were scored from 0 to 3 points (one point each for not smoking, not drinking, and being physically active), the risk of depression showed a decreasing tendency as lifestyle scores increased from 0 (reference) to 1 (HR = 0.69, 95% CI: 0.55-0.83), 2 (HR = 0.60, 95% CI: 0.50-0.76), and 3 (HR = 0.55, 95% CI: 0.45-0.68) points. Conclusions: Smoking cessation and alcohol abstinence can reduce the risk of depression in gastric cancer patients who undergo gastrectomy. [Table: see text]
Immunohistochemical and genetic profiles do not predict behavior of mixed hepatocellular intrahepatic cholangiocarcinoma.
Authors: Santiago Sucre, Rodrigo Paredes, Mary Linton Bounetheau Peters
Journal: Journal of Clinical Oncology (2023)

516 Background: Combined hepatocellular intrahepatic cholangiocarcinoma (HCC CC) is a rare tumor defined by pathologic characteristics of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Immunohistochemical (IHC) and genetic profiles (GP) are used for diagnosis and therapeutic decisions, however often mixed tumors are treated as ICC given the presumption this subtype dominates response. Recent studies challenged this practice by demonstrating improved response with immune oncology (IO) therapy. Methods: We identified nine patients with biopsy-proven mixed HCC CC between September 2013 and March 2022. We classified IHC as related to either HCC (HepPar1, Glypican3, CD10, Glutamine Synthetase, CEA, AFP, Arginase1) or ICC (CK19, CK7, CK20, CDX2, Mucicarmine, CA9, MOC31). GP results were classified as HCC-related (TERT, CTNNB1, MYC) or ICC-related (ARID1A, FGFR2, IDH1). Treatment selection, duration of response, and survival were recorded. Results: All subjects had a mix of IHC markers, although six had a preponderance of HCC-related IHC. GP information was available for seven patients, of whom six demonstrated mutations relating only to HCC, and one demonstrated mutations relating only to ICC. All sequenced tumors were MSS, and six of the seven were TMB low. Four subjects used only liver directed therapy for small intrahepatic tumors. Four subjects underwent systemic therapy, a mix of HCC and ICC regimens, three of whom used IO agents. Median survival was 12 months. Conclusions: HCC CC tumor profiling by IHC and GP was more closely aligned with HCC than ICC. However, the median survival for these patients was lower than expected for liver-restricted HCC, more congruent with an ICC phenotype. Although liver-directed therapy was used, the duration of response was shorter than expected for HCC, even in HCC-like tumors. For those receiving systemic therapy, most subjects did not achieve median response with any regimen. Although a previous case series showed good response to IO agents, in our cohort we did not see this effect. In this series, mixed HCC CC was more aggressive than HCC, with largely poor response to both liver directed and systemic therapy. We have insufficient information to correlate systemic treatment response relative to IHC or GP.[Table: see text]
Camrelizumab plus apatinib for immunochemotherapy-treated advanced esophageal squamous cell carcinoma: Preliminary results of cohort 2 in CAP 02 study.
Authors: Feng Wang, Junsheng Wang, Xiangrui Meng, Zhiquan Luo, Jin Xia, Yong-Gui Hong, Ping Lu, Yinghua Ji, Zheng-Zheng Shan, Qingxia Fan
Journal: Journal of Clinical Oncology (2023)

384 Background: CAP 02 study (NCT03736863) is a single-arm phase 2 study to evaluate the efficacy and safety of camrelizumab plus apatinib (a VEGFR2 inhibitor) as second-line treatment in patients with advanced esophageal squamous cell carcinoma (ESCC). Cohort 1 has been published recently, which enrolled patients who progressed after or were intolerant to first-line chemotherapy. The results showed an encouraging median overall survival (OS) of 15.8 months. Here, we reported the preliminary results of cohort 2. Methods: Cohort 2 enrolled unresectable locally advanced, locally recurrent, or metastatic ESCC patients aged 18-75 years with ECOG performance status of 0-1 who had progression on or were intolerant to first-line immunochemotherapy. The disease should be controlled without progression for at least three months during the first-line treatment. Patients received camrelizumab (200 mg Q2W) and apatinib (250 mg QD) until disease progression, intolerable toxicity, or withdrawal for other reasons. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate, progression-free survival (PFS), duration of response, time to response, OS, 3/6-month PFS rates, 6/9/12-month OS rates, and safety. Results: At the data cutoff (Sep 21, 2022), 33 of the planned 40 patients with an average of 68 years old had been enrolled, including 24 (73%) males and 24 (73%) patients with an ECOG PS score of 1. Twenty-one patients (64%) were previously treated with camrelizumab combined chemotherapy and 12 with other immunochemotherapy. Among the 17 evaluable patients, seven had the best overall response of partial response and nine with stable disease; the ORR was 41%. A total of 22 patients (67%) had treatment-related adverse events (TRAEs), with 12 patients (36%) with grade≥3. The most common TRAEs included white blood cell count decreased (11 patients, 33%), hypokalaemia (9, 27%), and alanine aminotransferase increased (8, 24%). Conclusions: Current results suggested the preliminary efficacy of second-line camrelizumab plus apatinib in patients with immunochemotherapy-treated advanced ESCC, with an acceptable safety profile. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03736863 .
Epidemiology and survival analysis of non-GIST GI sarcomas: A two-decade analysis of SEER database.
Authors: Snigdha Nutalapati, Reema Anil Patel, Quan Chen, Bin Huang
Journal: Journal of Clinical Oncology (2023)

812 Background: Primary adult non-GIST (gastrointestinal stromal tumors) gastrointestinal sarcomas are rare, accounting for 1-2% of all GI malignancies. Given the paucity of literature, we aimed to study the epidemiology and clinical outcomes of these sarcomas. Methods: National SEER-18 registry database was analyzed from 2001 to 2019 to identify non-GIST-GI sarcomas among adults aged 20 years and older. Demographics and clinical factors, including age at diagnosis, gender, race, primary cancer site, histology group, tumor grade and treatment, were examined in descriptive analysis. Log-rank tests, KM plots and Cox regression were utilized for observed survival analysis. P-value of &lt;0.01 was considered statistically significant. Retroperitoneal sarcomas were excluded. Results: A total of 1277 non-GIST-GI sarcomas were identified, 53.6% were male. Common primary sites include small intestine (32.4%), stomach (27.0%), colon (23.0%), esophagus (8.4%), rectum (8.3%) and anus (0.9%). Most common histological subtype was leiomyosarcoma (52.8%) followed by sarcomatoid carcinoma (10.6%), spindle cell sarcoma (6.2%), carcinosarcoma (5.9%), liposarcoma (5.2%) and angiosarcoma (4.7%). Surgery only was the most common treatment received (61.4%). Stratified by primary tumor site, five-year survival rate was highest for colon (46%; 95% CI 40-52) followed by anus (HR 44%; 95% CI 15-70), stomach (HR 42%; 95% CI 36-47), rectum (HR 36%; 95% CI 27-46), small intestine (HR 36%; 95% CI 31-41) and esophagus (HR 30%; 95% CI 21-38).Similarly, for common histological subtypes 5-year survival was highest for liposarcoma (HR 56%; 95% CI 43-68) followed by leiomyosarcoma (HR 46%; 95% CI 42-50) and spindle cell sarcoma (HR 36%; 95% CI 25-47) and lowest for carcinosarcoma (HR 15%; 95% CI 8-25) followed by sarcomatoid carcinoma (HR 17%; 95% CI 11-24), and angiosarcoma (HR 17%; 95% CI 9-28).On multivariate cox regression analysis, factors associated with unfavorable prognosis were male gender (HR 1.21; 95% CI 1.06-1.39), small intestine (HR 1.38; 95% CI 1.15-1.65) sarcomatoid sarcoma (HR 1.42; 95% CI 1.06-1.92), poorly differentiated tumors(HR 2.90; 95% CI 1.99-2.43). Esophageal primary (HR 0.66; 95% CI 0.49-0.87) and leiomyosarcoma (HR 0.81; 95% CI 0.70-0.94) had a favorable prognosis. Conclusions: Non-GIST-GI sarcomas are very rare with slight male predominance and more than three quarters of cases diagnosed among 55 years and older. Leiomyosarcoma was the most common subtype and small intestine was most common primary site. Overall liposarcoma had the highest five year survival rate and carcinosarcoma had the lowest.On multivariate analysis male gender, small intestinal primary, sarcomatoid carcinoma had unfavorable prognosis.
Efficacy of fecal microbiota transplantation in patients with anti-PD-1–resistant/refractory gastrointestinal cancers.
Authors: Zhi Peng, Xiaotian Zhang, Tong Xie, Siyuan Cheng, Zihan Han, Shulin Wang, Zongwen Ban, Xiaomin Xu, Zhengnong Zhu, Jing Zhu, Xiaochen Yin, Sumin Li, Lin Shen
Journal: Journal of Clinical Oncology (2023)

389 Background: Gut microbiome that changed the response to anti-PD-1 therapy (aPD-1) against melanoma by fecal microbiota transplantation (FMT) has been reported. To investigate whether resistance to aPD-1 against gastrointestinal (GI) cancers can be overcome by FMT, this single arm, open label, investigator-initiated trial explored the efficacy of combination of FMT + nivolumab in patients with aPD-1 resistant/refractory (aPD-1r)-GI cancers. Methods: Ten patients were planned to be enrolled. Interim analysis was planned when at least one patient demonstrated effective outcome. FMT capsules were from healthy donors. FMT capsules (CFU≥1×10 12 ) were administered in the first week. Nivolumab (3mg/kg, q2w) combined with a maintenance dose of FMT capsules (CFU≥1.5×10 11 ) were started at Week 2 and continued for 6 cycles or until progress of disease (PD) after 3 cycles of treatment. If patient responded to the treatment and would be benefit from the treatment beyond 6 cycles, patients would enter the Expended Excess Program to continue the therapy. RECIST v1.1 evaluation was performed every 3 cycles. Stool samples were collected every 2 weeks for metagenomic analysis of gut microbiota. Results: 8 aPD-1r patients were enrolled and finished the study by the time of this analysis. Nivolumab + FMT therapy was well tolerated. No serious adverse reaction was observed. 8 patients completed 3 cycles of treatment. Metagenomic analysis of gut microbiota from Responders (R) and Non-Responders (NR) groups revealed the gut microbial composition of R group is significantly closer to that of the donor than NR group, which indicated much better colonization of donor microbiota in R. Alpha diversity was significantly higher in R than that in NR, along with a set of differential bacterial species and biological process functions including dTMP biosynthetic process enriched, suggesting gut microbiome’s potential role in the treatment. The flow cytometry analysis indicated a significant increase of IFN-ϒ+ cells in PBMCs in R at Day 8 after FMT (the highest increase during the study), before combination therapy had started. A significant increase in Ki-67+ cells in PBMCs was also observed in the R group. Relative abundance of differential bacterial species enriched in R were found to be significantly negative correlated with tumor markers like CA199 and tumor volume, and some were positively correlated with expression of CD3+CD4+ cells and CD3+CD8+ cells. Conclusions: FMT+aPD-1 may overcome the resistance to aPD-1 against GI cancer via changing gut microbiota structure. Trial registration number: NCT04130763. Keywords: gastrointestinal cancers; fecal microbiota transplantation; anti-PD-1 therapy. Clinical trial information: NCT04130763 .
Tumor mutations associated with outcomes in colorectal peritoneal metastases.
Authors: Abhineet Uppal, Michael White, George J. Chang, Fadl A. Zeineddine, Mohammad A. Zeineddine, Abdelrahman M.G. Yousef, Christopher Scally, Keith F. Fournier, Timothy E. Newhook, Y. Nancy You, Jason Willis, Scott Kopetz, John Paul Y.C. Shen
Journal: Journal of Clinical Oncology (2023)

196 Background: The association between tumor mutations beyond KRAS and BRAF for patients with peritoneal metastases (PM) from colorectal cancer (CRC) are poorly understood. Here we describe these associations with survival after diagnosis of PM. Methods: CRC patients with PM with or without synchronous liver or lung metastases treated at a single institution from 2016 to 2020 were retrospectively studied. Standard of care next-generation sequencing was performed on tissue specimens with a targeted panel of genes frequently mutated in cancer. Clinical data, including survival and last contact, were obtained from medical records. Multivariate Cox regression was used to identify associations between overall survival after diagnosis of PM (OS) with clinical, histopathologic and somatic mutation data. Results: Of 526 PM patients, 179 (34.2%) also had synchronous liver metastases, and these patients had worse OS compared to PM alone (HR 1.67, [1.26-2.22], p=0.0003). Lung metastases were identified in 57 (10.8%) and were not associated with worse OS (HR 1.34, [0.90-1.97], p=0.15). Poorly differentiated grade (HR 2.08, [1.42-3.04], p=0.0002), mucinous histology (HR 1.44, [1.07-1.94], p=0.016), male gender (HR 1.37, [1.05-1.78), p=0.019), and age (HR 1.02, [1.01-1.04], p=0.004) were independently associated with OS. Tumor sequencing data was available for 442 (87%) patients. TP53 was the most common mutation (61.5% of patients) and was associated with decreased OS (HR=1.51 [1.12-2.02], p=0.005). BRAF mutation (85% of which were V600E) was identified in 9.7% of patients and was also associated with decreased OS (HR=1.88 [1.23-2.86], p=0.003). In contrast, PTEN mutation (4.3%) was associated with improved OS (0.41 (0.17-0.99), p=0.049), while both KRAS (51.4%) and SMAD4 mutations (16%) were not (KRAS: HR 0.94, [0.72-1.24], p=0.68; SMAD4: HR 0.78, [0.53-1.16], p=0.21). Conclusions: Mutational data for PM patients has a distinct profile and unique associations with OS when compared to other sites of metastatic disease. TP53 and BRAF mutations were associated with worse survival, while PTEN mutation was associated with improved OS. KRAS mutation was more prevalent than expected in an unselected cohort, and not associated with OS. A better understanding of PM-specific associations with survival may influence treatment strategies for this difficult disease site.